2017 Grants - Serrano-Pozo

Transcriptomic Changes of Astrocytes in Alzheimer's Disease

2017 Alzheimer’s Association Clinical Fellowship (AACF)

How do support cells in the brain called astrocytes impact nerve cell function in Alzheimer’s disease?

Background
Astrocytes are the most numerous cell type in the brain and play an important role in supporting nerve cell function. Recent studies have shown that astrocytes can have both beneficial and harmful effects on the brain in Alzheimer’s disease. Normally astrocytes help maintain nerve cells synapses – the tiny junctures through which nerve cells communicate with each other. However, in Alzheimer’s disease certain astrocytes become “reactive” and can release molecules that can damage synapses. More research is needed to better understand what triggers astrocytes to become reactive and how this relates to brain changes associated with Alzheimer’s disease.

Research Plan
Alberto Serrano-Pozo, M.D., Ph.D. and colleagues will collect astrocytes from human brain tissue of people who had Alzheimer’s disease. They will use new genetic techniques to analyze the astrocytes’ “transcriptome” which is the complete instructions for which genes should be turned on and off. They will compare the transcriptome of astrocytes from the Alzheimer’s brains to the transcriptome of astrocytes from healthy brains to understand what genes may be involved in causing astrocytes to become reactive and release toxic molecules. They are particularly interested to understand the unique characteristics of astrocytes that are located near amyloid plaques and tau tangles in the brain, which could be a trigger for abnormal gene activity. They hypothesize that reactive astrocytes near plaques and tangles may contribute to the loss of synapses on nearby nerve cells.

Impact
The results of these studies could provide new information on the role of astrocytes in the healthy brain and in Alzheimer’s disease. This work could also shed new light on how plaques and tangles in the brain may influence the characteristics of astrocytes. Ultimately, this information could reveal new targets for the development of treatments that regulate astrocyte function to help slow or prevent Alzheimer’s disease.